It occurs naturally in the peyote cactus (Lophophora williamsii), the San Pedro cactus (Echinopsis pachanoi) and the Peruvian Torch cactus (Echinopsis peruviana), and it is also found in a number of other members of the Cactaceae. It can be extracted from these sources. Mescaline was first isolated and identified in 1897 by the German Arthur Heffterand first synthesized in 1919 by Ernst Späth.

For the drug to take effect, disk-shaped buttons are cut from the roots, on the top of the cactus, and dried. It is chewed to produce its effect or soaked in water for an intoxicating drink. The effective human dosage is 0.3–0.5 grams, with the effects lasting for up to 12 hours. Users typically experience visual hallucinations and radically altered states of consciousness, often experienced as pleasurable and illuminating but occasionally as accompanied by feelings of anxiety or revulsion. It is not physically addictive.